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Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate

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Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate. / Mailer, Reiner K; Allende, Mikel; Heestermans, Marco; Schweizer, Michaela; Deppermann, Carsten; Frye, Maike; Pula, Giordano; Odeberg, Jacob; Gelderblom, Mathias; Rose-John, Stefan; Sickmann, Albert; Blankenberg, Stefan; Huber, Tobias B; Kubisch, Christian; Maas, Coen; Gambaryan, Stepan; Firsov, Dmitri; Stavrou, Evi X; Butler, Lynn M; Renné, Thomas.

In: BLOOD, Vol. 137, No. 10, 11.03.2021, p. 1392-1405.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Mailer, RK, Allende, M, Heestermans, M, Schweizer, M, Deppermann, C, Frye, M, Pula, G, Odeberg, J, Gelderblom, M, Rose-John, S, Sickmann, A, Blankenberg, S, Huber, TB, Kubisch, C, Maas, C, Gambaryan, S, Firsov, D, Stavrou, EX, Butler, LM & Renné, T 2021, 'Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate', BLOOD, vol. 137, no. 10, pp. 1392-1405. https://doi.org/10.1182/blood.2019004617

APA

Mailer, R. K., Allende, M., Heestermans, M., Schweizer, M., Deppermann, C., Frye, M., Pula, G., Odeberg, J., Gelderblom, M., Rose-John, S., Sickmann, A., Blankenberg, S., Huber, T. B., Kubisch, C., Maas, C., Gambaryan, S., Firsov, D., Stavrou, E. X., Butler, L. M., & Renné, T. (2021). Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate. BLOOD, 137(10), 1392-1405. https://doi.org/10.1182/blood.2019004617

Vancouver

Mailer RK, Allende M, Heestermans M, Schweizer M, Deppermann C, Frye M et al. Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate. BLOOD. 2021 Mar 11;137(10):1392-1405. https://doi.org/10.1182/blood.2019004617

Bibtex

@article{6b04fb143e1b4de5a60014266e4e4ba8,
title = "Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate",
abstract = "Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in platelets and was implicated in thrombosis in vivo. We used bioinformatic analyses of omics data to identify XPR1 as a major phosphate transporter in platelets. XPR1 messenger RNA and protein expression inversely correlated with intracellular polyphosphate content and release. Pharmacological interference with XPR1 activity increased polyphosphate stores, led to enhanced platelet-driven coagulation, and amplified thrombus formation under flow via the polyphosphate/factor XII pathway. Conditional gene deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and augmented activated platelet-driven pulmonary embolism without increasing bleeding in mice. These data identify platelet XPR1 as an integral regulator of platelet polyphosphate metabolism and reveal a fundamental role for phosphate homeostasis in thrombosis.",
author = "Mailer, {Reiner K} and Mikel Allende and Marco Heestermans and Michaela Schweizer and Carsten Deppermann and Maike Frye and Giordano Pula and Jacob Odeberg and Mathias Gelderblom and Stefan Rose-John and Albert Sickmann and Stefan Blankenberg and Huber, {Tobias B} and Christian Kubisch and Coen Maas and Stepan Gambaryan and Dmitri Firsov and Stavrou, {Evi X} and Butler, {Lynn M} and Thomas Renn{\'e}",
year = "2021",
month = mar,
day = "11",
doi = "10.1182/blood.2019004617",
language = "English",
volume = "137",
pages = "1392--1405",
journal = "BLOOD",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "10",

}

RIS

TY - JOUR

T1 - Xenotropic and polytropic retrovirus receptor 1 regulates procoagulant platelet polyphosphate

AU - Mailer, Reiner K

AU - Allende, Mikel

AU - Heestermans, Marco

AU - Schweizer, Michaela

AU - Deppermann, Carsten

AU - Frye, Maike

AU - Pula, Giordano

AU - Odeberg, Jacob

AU - Gelderblom, Mathias

AU - Rose-John, Stefan

AU - Sickmann, Albert

AU - Blankenberg, Stefan

AU - Huber, Tobias B

AU - Kubisch, Christian

AU - Maas, Coen

AU - Gambaryan, Stepan

AU - Firsov, Dmitri

AU - Stavrou, Evi X

AU - Butler, Lynn M

AU - Renné, Thomas

PY - 2021/3/11

Y1 - 2021/3/11

N2 - Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in platelets and was implicated in thrombosis in vivo. We used bioinformatic analyses of omics data to identify XPR1 as a major phosphate transporter in platelets. XPR1 messenger RNA and protein expression inversely correlated with intracellular polyphosphate content and release. Pharmacological interference with XPR1 activity increased polyphosphate stores, led to enhanced platelet-driven coagulation, and amplified thrombus formation under flow via the polyphosphate/factor XII pathway. Conditional gene deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and augmented activated platelet-driven pulmonary embolism without increasing bleeding in mice. These data identify platelet XPR1 as an integral regulator of platelet polyphosphate metabolism and reveal a fundamental role for phosphate homeostasis in thrombosis.

AB - Polyphosphate is a procoagulant inorganic polymer of linear-linked orthophosphate residues. Multiple investigations have established the importance of platelet polyphosphate in blood coagulation; however, the mechanistic details of polyphosphate homeostasis in mammalian species remain largely undefined. In this study, xenotropic and polytropic retrovirus receptor 1 (XPR1) regulated polyphosphate in platelets and was implicated in thrombosis in vivo. We used bioinformatic analyses of omics data to identify XPR1 as a major phosphate transporter in platelets. XPR1 messenger RNA and protein expression inversely correlated with intracellular polyphosphate content and release. Pharmacological interference with XPR1 activity increased polyphosphate stores, led to enhanced platelet-driven coagulation, and amplified thrombus formation under flow via the polyphosphate/factor XII pathway. Conditional gene deletion of Xpr1 in platelets resulted in polyphosphate accumulation, accelerated arterial thrombosis, and augmented activated platelet-driven pulmonary embolism without increasing bleeding in mice. These data identify platelet XPR1 as an integral regulator of platelet polyphosphate metabolism and reveal a fundamental role for phosphate homeostasis in thrombosis.

U2 - 10.1182/blood.2019004617

DO - 10.1182/blood.2019004617

M3 - SCORING: Journal article

C2 - 32932519

VL - 137

SP - 1392

EP - 1405

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 10

ER -